Funds are requested to purchase an Applied Biosystems Model 3730 (48 capillary) DNA Analyzer (referred to below as ABI 3730), together with software, peripherals and service agreement that will allow the unit to perform to our anticipated level of throughput and speed. At present and for several years to come, the ABI 3730 represents the standard for automated DNA sequencing, with over a decade of research and development in software and sequencing chemistry behind it. The ABI 3730 is a high-throughput DNA sequencer. For standard read sequencing runs (around 650 bases per run), the 3730 can run about 1150 samples/day, for a total of approximately 750,000 bases sequenced per day. The instrument's capacity will be adequate to handle the anticipated demands for sequencing, including the need to accommodate the rapidly expanding faculty of the Kimmel Cancer Center (KCC) following the recruitment of its new Director, Dr. Richard G. Pestell. At present, our sequencing needs are being met by old equipment which is outmoded and no longer repairable. The manufacturer no longer will support this old equipment, service contracts are no longer available, nor are replacement parts. Because of the increasing age and decreasing reliability of our old sequencing equipment, along with the increasing demand for sequencing from current researchers and the large number of new investigators (up to 20) being recruited for the KCC under its new Director, we will require new state-of-the-art DNA sequencing equipment. In addition, features such as capability to perform SNP/mutation analysis by single-base extension, will be required. All these needs are met in the ABI 3730 (48 capillary) DNA Analyzer, which can perform DNA sequencing, single base extension and fluorescent fragment analysis (GeneScan) on an array of 48 capillaries. The long term objective of this application is the elucidation of the molecular basis for several human diseases, including cancer, cardiovascular and renal disease, skin disease, connective tissue disease, and diabetes. In all these areas, the specific aims focus on DNA sequencing to determine the genetic alterations underlying the disease pathology. Relevance. Central to understanding the molecular basis of human diseases is the determination of the changes at the gene level that underlie the disease. In order to do this, funds are requested to purchase a state-of-the-art DNA sequencer that will allow us to determine the specific genetic changes involved in several human diseases, including cancer, heart and kidney disease, skin disease, connective tissue disease, and diabetes. The information acquired will help to improve prevention, diagnosis, and treatment of these serious and often fatal diseases. [unreadable] [unreadable] [unreadable]